CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Serum Tumor Markers for Malignancies

Policy governing when measurement of specific serum tumor markers is considered covered for diagnosis, monitoring, surveillance, and follow-up for various malignancies for BlueCross BlueShield of Tennessee members.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicySerum Tumor Markers for Malignancies

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionVerify member benefits at the time of request and apply marker-specific coverage criteria when submitting claims.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

Dozenstumor markers referenced as in common use

Quarterlypermitted frequency for designated markers

~20+CPT/HCPCS codes listed

MultipleProprietary tests named

NumerousReferences listed

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inv-01: Covered Marker Indications

Covered when indications listed for specific serum tumor markers

Covered marker-indication pairs: Measurement of specified serum tumor markers meets coverage criteria when used for the listed indications (diagnostic workup, monitoring during treatment, surveillance, post-treatment follow-up) as detailed in the policy for each marker and cancer type.see individual marker entries in document

Examples: AFP for hepatocellular carcinoma screening/workup/surveillance; CA-125 for ovarian cancer monitoring; CA19-9 for pancreatic, biliary, ampullary cancers; CEA for colorectal/appendiceal/rectal cancer surveillance; beta-HCG for gestational trophoblastic disease and testicular cancers; B2M for multiple myeloma and B-cell lymphomas; LDH for lymphomas; calcitonin for medullary thyroid carcinoma; serum free light chain up to monthly for multiple myeloma.

inv-02: Not Medically Necessary / Not Covered

Not covered indications

Not covered scenarios: Use of the listed biomarkers for cancer indications not discussed in the policy does not meet coverage criteria.

All other serum tumor markers not addressed and analysis of proteomic serum patterns for screening/detection do not meet coverage.

All serum tumor markers or panels that are not specifically addressed in this policy do not meet coverage criteria. This includes any panels composed of multiple serum markers as well as individual markers not listed in the covered-indications section. In addition, analysis of proteomic patterns in serum for cancer screening or detection is explicitly not considered medically necessary and does not meet coverage criteria.

Procedure and billing codes shown in this policy are provided solely as a general reference and may not be exhaustive. Providers should verify coding and submit the most appropriate CPT/HCPCS code(s) for the test performed; inclusion in this document does not guarantee coverage.

For any cancer indications not expressly discussed in the policy, measurement of biomarkers—whether reported as single analytes or as part of multi‑analyte panels—does not meet coverage criteria and may be denied.

Marker-Specific Covered Indications

inv-26: Numerous marker-specific cancer indications

Numerous marker-specific cancer indications — individual marker examples and typical uses; frequency notes where specified

Marker examples: Alkaline phosphatase (ALP): workup and monitoring for bone neoplasms; systemic light chain amyloidosis initial workup.

[see policy for specifics]

Marker examples: Alpha-fetoprotein (AFP): hepatocellular carcinoma screening, workup for confirmed HCC, surveillance (every 3-6 months for 2 years, then every 6 months).

Marker examples: Cancer antigen 19-9 (CA 19-9): workup and surveillance for ampullary adenocarcinoma, intrahepatic and extrahepatic cholangiocarcinoma, gallbladder cancer, and resected ampullary cancer (surveillance every 3-6 months for 2 years, then every 6-12 months as clinically indicated).

Abnormal measurements should be trended.

Marker examples: Cancer antigen 15-3 and 27.29 (CA 15-3/27.29): monitoring metastatic breast cancer; workup for occult primary and monitoring/follow-up for response.

Marker examples: Carcinoembryonic antigen (CEA): baseline workup, monitoring, and surveillance for colon cancer (every 3-6 months for 2 years, then every 6 months for total of 5 years); baseline/monitoring for appendiceal, gallbladder, cholangiocarcinoma, ovarian cancers and selected others.

Post-surgical medullary carcinoma surveillance 2-3 months postoperative, then every 6-12 months.

Marker examples: Beta human chorionic gonadotropin (beta-hCG): initial workup, during and post treatment (no more than weekly when appropriate), follow-up/surveillance (no more than monthly for 12 months) for gestational trophoblastic neoplasia; surveillance for malignant germ cell tumors and testicular cancers (no more than every 2 months early after treatment).

Marker examples: Beta-2 microglobulin (B2M): workup for B-cell lymphomas, chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma (initial diagnostic workup and follow-up/surveillance as needed), systemic light chain amyloidosis initial workup.

Marker examples: Calcitonin (CALCA): workup for medullary carcinoma and selected epithelial tumors; post-surgical evaluation and monitoring/surveillance (2-3 months postoperative, then every 6-12 months); screening at diagnosis for MEN2 when clinically indicated.

Marker examples: Inhibin (INHA): workup for adrenocortical carcinoma and ovarian cancers; monitoring/follow-up for ovarian cancer types including malignant germ cell tumors with specified surveillance frequencies (e.g., no more than every 2 months for first 2 years for germ cell tumors).

Marker examples: Lactate dehydrogenase (LDH): workup for various B-cell lymphomas, bone neoplasms, chronic lymphocytic leukemia/small lymphocytic lymphoma (including at transformation).

Marker examples: Serum free light chain: initial diagnostic workup and surveillance for multiple myeloma (up to once per month); also for systemic light chain amyloidosis initial workup.

Frequency: up to once per month for multiple myeloma.

Marker examples: Troponin T: initial diagnostic workup for systemic light chain amyloidosis.

Marker examples: Tryptase: initial diagnostic workup for systemic mastocytosis.

inv-27: Use of FDA-approved serum tumor marker tests and laboratory-developed tests for clinical assessment

Regulatory note regarding test types

LDT and FDA-approved tests: There are numerous FDA-approved tests for serum tumor markers; many laboratories also use laboratory-developed tests (LDTs) that are performed in-house.

LDTs are regulated by CMS as high-complexity tests under CLIA '88; they are not FDA approved or cleared but FDA clearance is not required for clinical use.

inv-28: References to serologic proteome analysis and autoantibodies for cancer detection

Citation-only references related to serologic proteome analysis and autoantibodies for cancer detection

Citation: Serological proteome analysis: Qin J et al. (2020) — Using Serological Proteome Analysis to Identify and Evaluate Anti-GRP78 Autoantibody as Biomarker in the Detection of Gastric Cancer. J Oncol 2020;9430737. https://doi.org/10.1155/2020/9430737

This reference is listed for informational purposes; the policy states proteomic pattern analysis in serum for cancer screening/detection does not meet coverage criteria.

Surveillance and Testing Frequency Limits

Examples of specified frequencies

CA19-9 / CEA surveillanceEvery 3–6 months for the first 2 years, then every 6–12 months (as clinically indicated)

Malignant germ cell tumor surveillance (testicular — nonseminoma and pure seminoma)No more than every 2 months during the first 2 years

Serum free light chain (multiple myeloma)Up to once per month for surveillance

AFP (hepatocellular carcinoma)Surveillance every 3–6 months for 2 years, then every 6 months

Surveillance frequency examples

Quarterly measurement allowanceExcept where otherwise specified, quarterly measurement of designated serum tumor markers is permitted for follow-up, monitoring, and/or surveillance

Monthly limit exampleSerum free light chain surveillance allowed up to once per month for multiple myeloma

Bi-monthly constraint for testicular cancerPost-treatment surveillance for testicular nonseminoma and pure seminoma: no more than every 2 months

Two-year then extended intervalFor some markers (e.g., CA19-9, CEA): every 3–6 months for 2 years then every 6–12 months

Coding and Procedure Codes

Applicable CPT/HCPCS Procedure CodesCPT

81479	Unlisted molecular pathology procedure.
81599	Unlisted multianalyte assay with algorithmic analysis.
82105	Alpha-fetoprotein (AFP); serum.
82107	Alpha-fetoprotein (AFP); AFP-L3 fraction isoform and total AFP (including ratio).
82232	Beta-2 microglobulin.
82308	Calcitonin.
82378	Carcinoembryonic antigen (CEA).
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
83521	Immunoglobulin light chains (i.e., kappa, lambda), free, each.
83615	Lactate dehydrogenase (LD), (LDH).

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Covered CPT/HCPCS codes (partial list)CPT

81479	Unlisted molecular pathology procedure.
81599	Unlisted multianalyte assay with algorithmic analysis.
82105	Alpha-fetoprotein (AFP); serum.
82107	Alpha-fetoprotein (AFP); AFP-L3 fraction isoform and total AFP (including ratio).
82232	Beta-2 microglobulin.
82308	Calcitonin.
82378	Carcinoembryonic antigen (CEA).
83520	Immunoassay for analyte other than infectious agent antibody or infectious agent antigen; quantitative, not otherwise specified.
83521	Immunoglobulin light chains (i.e., kappa, lambda), free, each.
83615	Lactate dehydrogenase (LD), (LDH).

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Covered CPT/HCPCS codes (proprietary and tumor markers)CPT | HCPCS

86301	Immunoassay for tumor antigen, quantitative; CA 19-9.
86304	Immunoassay for tumor antigen, quantitative; CA 125.
86305	Human epididymis protein 4 (HE4).
86316	Immunoassay for tumor antigen, other antigen, quantitative (e.g., CA 50, 72-4, 549).
86336	Inhibin A.
0003U	Oncology (ovarian) biochemical assays of five proteins, algorithm reported as a likelihood score (Overa/OVA1 Next Generation).
0092U	Oncology (lung), three protein biomarkers with algorithm reported as risk score (REVEAL Lung Nodule Characterization).
0163U	Oncology (colorectal) screening, ELISA of 3 plasma or serum proteins with proprietary algorithm (BeScreened).
0404U	Oncology (breast), semiquantitative measurement of thymidine kinase activity reported as risk of disease progression (Divitum Tka).
G0327	Colorectal cancer screening; blood-based biomarker.

None listed (coding examples)

Coding examplesNone listed

ThresholdsNone listed

NotesNo specific exceptions or alternate coding thresholds are provided in this section of the policy

Provider Actions and Billing Considerations

Note

Literature references and guidance

This section contains literature references cited in the policy and does not itself establish additional coverage criteria. Providers should consult the referenced studies and guideline documents for clinical context when preparing documentation.

Documentation Required

Guideline references (NCCN and others)

References include NCCN resources and other guideline documents (see citations) that may inform documentation expectations and clinical interpretation; these references are cited for informational purposes only and do not alter the policy's stated coverage rules.

Prior Authorization

Benefit verification required

Benefit verification is required; application of coverage criteria depends on the member's specific benefits at the time of service. Check applicable Medicare and Medicaid specifications where relevant.

Billing Rule

Proprietary tests identified

Several proprietary tests are identified in the procedure-code reference. Examples include: Overa™ (OVA1 Next Generation) — Aspira Labs/Vermillion; REVEAL Lung Nodule Characterization — MagArray, Inc.; BeScreened™-CRC — Beacon Biomedical Inc.; Divitum®Tka — Biovica Inc. Be aware of unique billing and algorithm-reporting considerations for these proprietary assays.

Billing Rule

Unlisted assay coding and coding reminder

Unlisted molecular (CPT 81479) and unlisted multianalyte assay codes (CPT 81599), and other unlisted chemistry codes (CPT 84999) appear in the CPT list. These are reference-only; verify with the payer whether prior authorization is required and confirm correct coding prior to claim submission.

CPT 81479 — Unlisted molecular pathology procedure
CPT 81599 — Unlisted multianalyte assay with algorithmic analysis
CPT 84999 — Unlisted chemistry procedure

Note

Procedural code reference reminder

Procedure codes appearing in the policy are provided only as a general reference and may not be exhaustive. Providers should validate code selection and ensure documentation supports the medical necessity of billed services.

Documentation Required

LDT regulatory note

Laboratory-developed tests (LDTs) referenced in this policy are regulated by CMS as high-complexity CLIA tests and are not FDA-approved or -cleared; FDA clearance/approval is not required for clinical use at this time. Labs performing LDTs are responsible for validation and CLIA compliance.

Step Therapy

Step therapy

No step therapy requirements are stated in the referenced policy chunks.

Prior Authorization

Prior authorization

Prior authorization requirements are not explicitly stated in these reference chunks; however, providers should confirm payer-specific prior authorization or coverage determination processes before ordering proprietary or unlisted assays.

OpenPayer

Serum Tumor Markers for Malignancies

Coverage Criteria

Marker-Specific Covered Indications

Surveillance and Testing Frequency Limits

Coding and Procedure Codes

Provider Actions and Billing Considerations

Ordering Requirements

Not Covered

Background

Definitions

References